Linked Life Data

10377349

Source:http://linkedlifedata.com/resource/pubmed/id/10377349

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
1999-7-15
pubmed:abstractText
In this report, we provide evidence that NGF and BDNF have functionally antagonistic actions on sympathetic neuron growth and target innervation, with NGF acting via TrkA to promote growth and BDNF via p75NTR to inhibit growth. Specifically, in cultured sympathetic neurons that themselves synthesize BDNF, exogenous BDNF inhibits and function-blocking BDNF antibodies enhance process outgrowth. Both exogenous and autocrine BDNF mediate this effect via p75NTR because (1) BDNF does not inhibit growth of neurons lacking p75NTR, (2) function-blocking p75NTR antibodies enhance NGF-mediated growth, and (3) p75NTR-/- sympathetic neurons grow more robustly in response to NGF than do their wild-type counterparts. To determine the physiological relevance of this functional antagonism, we examined the pineal gland, a well defined sympathetic target organ. BDNF is present in the pineal gland during target innervation, and incoming sympathetic axons are p75NTR positive. Moreover, the pineal glands of BDNF+/- and BDNF-/- mice are hyperinnervated with sympathetic fibers, and tyrosine hydroxylase (TH) levels are elevated. Increased tyrosine hydroxylase is also observed in the BDNF+/- carotid artery, another sympathetic neuron target. Thus, BDNF, made by sympathetic neurons and/or their target organs, acts via p75NTR to antagonize NGF-mediated growth and target innervation, suggesting that sympathetic target innervation is determined by the balance of positively and negatively acting neurotrophins present in developing and potentially mature targets.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0270-6474
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5393-408
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10377349-Animals, pubmed-meshheading:10377349-Antibodies, pubmed-meshheading:10377349-Autocrine Communication, pubmed-meshheading:10377349-Axons, pubmed-meshheading:10377349-Brain-Derived Neurotrophic Factor, pubmed-meshheading:10377349-Carotid Arteries, pubmed-meshheading:10377349-Cell Division, pubmed-meshheading:10377349-Cell Survival, pubmed-meshheading:10377349-Cells, Cultured, pubmed-meshheading:10377349-Gene Deletion, pubmed-meshheading:10377349-Genotype, pubmed-meshheading:10377349-Mice, pubmed-meshheading:10377349-Mice, Knockout, pubmed-meshheading:10377349-Nerve Growth Factors, pubmed-meshheading:10377349-Neurites, pubmed-meshheading:10377349-Neurons, pubmed-meshheading:10377349-Pineal Gland, pubmed-meshheading:10377349-Receptor, Nerve Growth Factor, pubmed-meshheading:10377349-Receptor, trkA, pubmed-meshheading:10377349-Receptors, Nerve Growth Factor, pubmed-meshheading:10377349-Signal Transduction, pubmed-meshheading:10377349-Sympathetic Nervous System, pubmed-meshheading:10377349-Tyrosine 3-Monooxygenase
pubmed:year
1999
pubmed:articleTitle
Functionally antagonistic interactions between the TrkA and p75 neurotrophin receptors regulate sympathetic neuron growth and target innervation.
pubmed:affiliation
Centre for Neuronal Survival, Montréal Neurological Institute, McGill University, Montréal, Québec, Canada, H3A 2B4.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't